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Changes at IHGT
The Institute for Human Gene Therapy
(IHGT) at Penn will no longer conduct human clinical trials, limiting
its scope to molecular, cellular and animal-model experimentation. This
change was announced by the University on May 24, following recommendations
made a month earlier by an external-review panel charged with examining
practices at the institute.
From now on, human-gene
experiments will be conducted by individual departments across the University,
with oversight by Penns Office of Regulatory Affairs. Though the
IHGTs focus will change, Dr. James M. Wilson, the John Herr Musser
Professor and Chair of Cellular and Molecular Engineering, will remain
director of the institute. In addition, an Institutional Review Board
(IRB) with expertise in evaluating gene therapy will be created, and the
entire system of IRBs at Penn will be studied to strengthen their ability
to protect patients vital interests.
Judith Rodin, president of the University, appointed the committee, composed
of scientists from peer institutions, after the U.S. Food and Drug Administration
put clinical trials on hold at the IHGT in January, four months after
the death of 18-year-old Jesse Gelsinger, a participant in a clinical
trial at the Institute. The FDAs investigation found numerous
and serious deficiencies in the monitoring and oversight of the
trial [Gazetteer, November/December, January/ February, March/April,
by Dr. William H. Danforth, a physician and chancellor emeritus of Washington
University in St. Louis, the committee met twice; interviewed 20 people
associated with clinical trials at IHGT, as well as Rodin and University
Provost Dr. Robert Barchi; and reviewed scores of documents.
In its report, the committee recommended that the University:
Evaluate the function and workload of Independent Review Boards at Penn
(which oversee issues of ethical decision-making in human experimentation),
making sure they include members who are knowledgeable about specialized
areas of research and that those boards share information, particularly
about adverse events, among different trials using similar therapies.
Review its conflict-of-interest policies, keeping in mind that perceived
as well as actual conflicts of interest make clinical trials more open
to suspicion and criticism.
Do everything possible to ensure that informed consent is obtained from
patients, following the letter as well as the spirit of
Consider whether it makes sense for an entire institute to be devoted
to gene therapy, and whether some services, such as the production of
vectors for clinical testing, would be better performed extramurally.
committee also made the following observations:
The IHGT scientists and the University appear committed to correcting
any deficiencies and complying with all regulations.
Detailed surveillance of clinical trials involving novel biologic therapies,
such as viral vectors, is essential. (Gelsinger had been injected with
a modified cold virus that was designed to deliver corrective genes
to the liver.)
To conduct independent clinical trialsthat is, trials that are
not sponsored and monitored by pharmaceutical companies or performed
in conjunction with other centers at other universities the University
must invest considerably more resources for regulatory compliance
than has historically been necessary for independent university-initiated
Even if all guidelines and regulations are followed, risk cannot be
eliminated from a clinical trial.
that the University was extremely grateful to the committee
members and praising their collective insight and considerable experience,
Rodin added: While we have moved aggressively in a variety of areas,
we recognize that we have considerable work to do to ensure that we structure
the best possible climate for clinical trials, one that always ensures
the interests of our patients are of paramount importance. We will continue
to work with our colleagues
and with regulators and with lawmakers
to accomplish this task.
University announced steps it has taken or will be taking, guided by the
Danforth-committee report and the interim recommendations of an internal-review
committee chaired by Provost Barchi. (The internal committee has been
examining all research involving human subjects at Penn and will continue
its work over the summer.) Among its steps and observations:
Though the IHGT was created in the belief that it made practical
sense to combine in one entity virtually all phases of basic science,
pre-clinical and clinical work in gene therapy, IHGT and the University
have now come to a different view. Experience has shown that it is very
difficult to align all required areas of expertise within a single integrated
institute or center.
As the IHGT was organized, there was considerable
consolidation of responsibility and authority in a single individual,
Rodin told the Gazette. Over time, Dr. Wilson was simply
overloaded with regard to responsibility, so one of our initial efforts
has been to reduce some of the day-to-day management and oversight responsibilities.
Various entities looking at this from many different directions came
to the same conclusionthat responsibility and authority needed
to be spread out somewhat.
Every clinical trial at Penn will be assessed by the Office of Regulatory
Affairs, which will hire additional staff, to determine the level of
monitoring required to comply with regulations. The limited number of
trials with no external sponsorship will be reviewed by a professional
contract research firm to determine if additional monitoring is needed.
The University is examining its IRB system to build on changes already
in place following an external review last summer, including a 24-hour
adverse-event hotline that was set up on February 1.
the University already has conflict-of-interest restrictions in place,
it will conduct a full review of its own policies.
am confident that the steps outlined today will help position Penn in
the future as a model environment for the conduct and oversight of all
types of clinical research, especially gene therapy, said Wilson,
the IHGTs director, in a written statement. He added that my
colleagues and I will refocus our efforts in the preclinical areawith
the goal of developing a foundation of science necessary to assure the
ultimate success of this field.
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Copyright 2000 The Pennsylvania
Gazette Last modified 6/28/00
Education and the Media
Plans Reconfigured by Press
is unwise to have bioethicists, involved in decision making, report
directly to one of the investigators or the Director of IHGT. So
read the report of a scientific panel appointed to review clinical-trial
procedures at Penns Institute for Human Gene Therapy (IHGT).
in truth, that did not happen at Penn, says Dr. Arthur Caplan, director
of the Center for Bioethics and the Trustee Professor of Bioethics
in Molecular and Cellular Engineering.
the University announced in May that, among other changes planned,
the center would become a free-standing department in the School
of Medicine, many of the resulting media reports
presented a picture of the Universitys widely-quoted ethicists
under the control of the much-scrutinized gene-therapy lab.
It is true, a
clearly irritated Caplan said, that the center will become a department,
chaired by him. Committees assigned to conduct its (routine) six-year
review recommended well before the Danforth committee reports release
that, in addition to the Center, there should also be a department
of bioethics to better support the bioethics-degree programs that
have formed in recent years. (The Centers faculty currently make
their tenure homes in various departments across the University.)
explains, The creation of a department has nothingrepeat nothingto
do with any statement of the Danforth committee, despite press reports
to the contrary.
members of the bioethics staff, including Caplan, have had their
tenure home in the Department of Molecular and Cellular Engineering,
which is chaired by Dr. James M. Wilson, the IHGTs director. But
the Center for Bioethics reports only to the dean of the medical
school. Caplan reports only to the dean and the University president,
and he is paid not through the department but the medical school.
Most of [the centers] 15 faculty have nothing to do with anything
related to genetics, he says.
to the suggestion of press reports, Caplan added, gene-therapy research
proposals went to Institutional Review Boards, not the bioethics
center, for formal review. There is a suggestion, in some press
accounts, that informal talk between bioethicists and gene
is a bad thing. This is completely stupid. Of course
we talk to our colleagues. We do, can, should, will and must.